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Partial reprogramming of melanoma cells mimics the phenotype switch and reveals SNAI3 as a novel invasion-associated marker

Knappe, Nathalie

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Abstract

The major challenge in anti-melanoma therapy is the tremendous plasticity of melanoma cells that leads to acquisition of resistance mechanisms and ultimately, to treatment failure and death. An emerging concept of melanoma cell plasticity is the so-called phenotype switch that describes the conversion of highly proliferative and little invasive into less proliferative and highly invasive melanoma cells. In vitro models of this phenotype switch are needed to understand the molecular mechanisms that drive cellular plasticity. Here, I demonstrate that abortion of reprogramming towards pluripotency converts HCmel17 melanoma cells into slowly proliferating cells with substantially elevated invasive potential. In detail, I show that reprogramming of murine melanoma cells is a stable process that induces gene expression changes in a time-dependent manner. Partially reprogrammed cells exhibit elevated invasive potential in vitro and increased lung colonization in vivo at day 12 after transgene induction. By global gene expression analysis in partially reprogrammed cells, I identified SNAI3 as a novel invasion-related marker in human melanoma. Protein expression of SNAI3 correlates with tumor thickness in primary melanomas and thus, might be of prognostic value for patient stratification. Partial reprogramming of murine melanoma cells is an innovative in vitro model to study phenotype switch-associated gene expression and identified SNAI3 as a novel invasion-related marker with potential for clinical application.

Item Type: Dissertation
Supervisor: Umansky, Prof. Dr. Viktor
Date of thesis defense: 24 March 2015
Date Deposited: 08 May 2015 11:19
Date: 2015
Faculties / Institutes: The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences
Subjects: 570 Life sciences
Controlled Keywords: Melanoma, Reprogramming, Snai3
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